Local anesthetics, such as lidocaine and ropivacaine, are fundamental to perioperative pain management. Beyond anesthesia, growing evidence indicates that local anesthetics may exert anticancer effects, potentially improving long-term oncologic outcomes by modulating tumor cell behavior and the perioperative environment. Surgery itself could promote metastasis via inflammatory and immunosuppressive pathways. However, the specific role and full therapeutic potential of local anesthetics in countering these effects are not fully defined. This review systematically synthesizes current understanding of the direct and indirect antitumor mechanisms of local anesthetics. We detail their direct inhibition of cancer cell proliferation through the induction of apoptosis and cell cycle arrest. The review also analyzes their indirect effects on the tumor microenvironment, which include enhancing antitumor immunity, attenuating surgery-induced stress and systemic inflammation, and inhibiting angiogenesis. We explore the potential synergy between local anesthetics and established cancer therapies, such as immunotherapy and targeted agents. Finally, the clinical evidence was appraised critically, discussing observational studies and the limited interventional trials linking regional anesthesia to improved survival, while addressing heterogeneity and confounding factors. By synthesizing mechanistic insights with clinical data, this review establishes a foundation for future research and highlights the translational potential of local anesthetics as adjuncts in perioperative cancer care.

Tumor dormancy is a clinically challenging but physiologically significant aspect of cancer development, characterized by disseminated tumor cells that persist in non-proliferative, quiescent state and frequently serving as a risk factor of recurrence. Although extensive progress has been made in understanding cancer progression and metastasis, strategies for reliably detecting and eliminating dormant tumor cells remain limited. This review aims to evaluate the current understanding of the molecular mechanisms underlying tumor dormancy, cellular quiscence, angiogenic processes, immune surveillance, and the complex roles of the tumor microenvironment, including extracellular matrix remodeling, metabolic adaptation and niche protection in tumor dormancy. Particular attention is given to the challenges associated with detecting and eliminating dormant cells, because these cells exhibit resistance to conventional therapies and reveal evasion of immune responses. Furthermore, we highlight peptide-based strategies as promising platforms for detection, modulation and elimination of dormant tumor cells. These include tumor-penetrating peptides, peptide-drug conjugates, self-assembling peptide nanostructures, and hydrogel–based delivery systems designed to disrupt dormancy-maintaining niches or sensitize dormant cells to therapeutic intervention. The review also provides a summary of recent preclinical and clinical developments in peptide-based treatments and outlines approaches to overcome translational challenges in targeting tumor dormancy. By integrating advances in peptide engineering with the biological principles of tumor dormancy, this review underscores the potential of peptide-based platforms to improve therapeutic outcomes and reduce cancer recurrence.

Cancer patients often have comorbidities that complicate treatment and worsen outcomes. Despite ongoing discussions, the interactions between comorbidities and cancer remain insufficiently understood. In addition, a widely accepted consensus on the document, assessment, and management of these comorbidities has not yet been established. This review aims to systematically synthesize current knowledge and propose a comprehensive framework for addressing these gaps. It summarizes the epidemiology and analyzes the clinical impacts of comorbidities on cancer patients, emphasizing the critical role of effective management of cancer comorbidities. It further examines key management challenges, including gaps in mechanisms and clinical evidence, the lack of precise assessment tools, limited management frameworks, and underdeveloped multidisciplinary collaborations. To address the complex interactions between cancer and comorbidities, this review proposes the establishment of Oncology-Comorbidity as a novel discipline and Oncology-Comorbidity Interaction Pathology as a theoretical framework. The assistance of artificial intelligence and real-world data, together with effective multidisciplinary collaborations, is emphasized as an essential management strategy. Comprehensive, patient-centered Life-Course Cohort Studies are identified as indispensable tools. Ultimately, this review aims to advance the understanding of cancer-comorbidity interactions, provide a roadmap for optimizing comorbidities management, and offer an effective pathway to improve prognosis and quality of life for cancer patients.

Ferroptosis is a regulated, iron-dependent form of cell death that has emerged as a promising therapeutic target for multiple cancers. However, its clinical translation faces significant challenges, particularly regarding precision and safety for cancer patients. Recent studies have identified RNA-binding proteins (RBPs) as novel regulators of tumor ferroptosis, extending beyond the established biochemical hallmarks and core defense mechanisms of ferroptosis. This review focuses on the core machinery of ferroptosis and the canonical functions of RBPs in cancer biology. We further present evidence demonstrating that RBPs play a critical role in coordinating iron, lipid, and amino acid metabolism to influence ferroptosis, highlighting the complex interplay between RBPs and ferroptotic processes. Building on these insights, we explore therapeutic opportunities targeting the RBP-ferroptosis axis from three perspectives: small molecules, synthetic lethality strategies, and drug delivery systems. Finally, we discuss the challenges and future prospects of RBP-based ferroptosis therapeutic strategies in cancer. Overall, this review underscores the significant role of RBPs in tumor ferroptosis and lays the groundwork for precision oncology approaches guided by ferroptosis, moving beyond the classical biochemical hallmarks and core defense systems.

Aging is the most potent independent risk factor for cancer initiation and progression, with these processes interacting through complex multi-level biological networks. While current research has identified key pathways, systematic integration of their synergistic effects and actionable clinical strategies remains underexplored. This review examines the complex nonlinear relationship between age and cancer risk, focusing on immune-cancer imbalance and late-stage rebalancing phenomena that accompany aging. It introduces the novel concept of premature cancer, emphasizing its distinct molecular features and microenvironment. During aging, genomic instability, dysregulated epigenetic modifications, immune senescence, and metabolic reprogramming are key biological changes that destabilize the aging-associated tumor microenvironment, fostering conditions conducive to cancer initiation and progression. The paper further explores the gene-immune-metabolic regulatory network formed through multidimensional interactions of these mechanisms, shedding light on how aging promotes cancer through this network. Additionally, translational therapeutic strategies, such as senescent cell eliminators and immunometabolic interventions, are discussed, with attention to challenges like the toxicity of senescent cell eliminators, the double-edged sword effect of nicotinamide adenine dinucleotide (NAD⁺) supplementation, and treatment resistance. This work provides new insights for precision prevention and treatment of age-related cancers, offering a foundation for advancing mechanistic research and promoting aging.